Experimental and molecular pathology最新文献_第3页

Corrigendum to “Characteristics of liver fibrosis associated with chronic Opisthorchis felineus infection in Syrian hamsters and humans” [Experimental and Molecular Pathology 110 (2019) 104274] “叙利亚仓鼠和人类慢性猫腹绦虫感染相关肝纤维化特征”[实验与分子病理学110(2019)104274]的勘误。

IF 3.7 4区医学 Q2 PATHOLOGY

Experimental and molecular pathology

Pub Date : 2025-12-01 DOI: 10.1016/j.yexmp.2025.104975

Anna V. Kovner , Maria Y. Pakharukova , Galina A. Maksimova , Viatcheslav A. Mordvinov

引用次数: 0

Retraction notice to “Interferon alpha-2b inhibits negative-strand RNA and protein expression from full-length HCV1a infectious clone” [Experimental and Molecular Pathology 76 (2004) 242–252]. “干扰素α -2b抑制全长HCV1a感染克隆负链RNA和蛋白质表达”的撤回通知[实验与分子病理学76(2004)242-252]。

IF 3.7 4区医学 Q2 PATHOLOGY

Experimental and molecular pathology

Pub Date : 2025-12-01 DOI: 10.1016/j.yexmp.2025.104999

Ramesh Prabhu , Virendra Joshi , Robert F. Garry , Frank Bastian , Salima Haque , Fredric Regenstein , Swan Thung , Srikanta Dash

引用次数: 0

Prevalence and clinical significance of CBP deficiency and disturbed CBP expression in human cancer 人类肿瘤组织中CBP缺乏及表达紊乱的患病率及临床意义

IF 3.7 4区医学 Q2 PATHOLOGY

Experimental and molecular pathology

Pub Date : 2025-12-01 DOI: 10.1016/j.yexmp.2025.105012

Victoria Chirico , Tabea Lenkeit , Seyma Büyücek , Katharina Möller , Florian Lutz , Florian Viehweger , Martina Kluth , Claudia Hube-Magg , Christian Bernreuther , Guido Sauter , Andreas H. Marx , Ronald Simon , Till Krech , Stefan Steurer , Christoph Fraune , Sarah Minner , Natalia Gorbokon , Maximilian Lennartz , Eike Burandt , Anne Menz , Nina Schraps

CBP (CREB-binding protein) is a ubiquitously expressed major histone modifier involved in the regulation of thousands of genes. In cancer, loss-of-function and overexpression can occur. To clarify the role of CBP expression, a tissue microarray containing 14,966 samples from 134 different tumor entities and 608 samples of 76 different normal tissues was analyzed by immunohistochemistry. In normal tissues, strong nuclear CBP staining was ubiquitously seen except of few cell types. Among 12,255 evaluable tumors, CBP staining was completely absent (CBP deficiency) in 226 (1.84 %) while 232 (1.89 %) showed only faint to moderate staining of a minority of cancer cells (substantial reduction, SR), 384 (3.13 %) weak, 3079 (25.12 %) moderate, and 8334 (68.00 %) strong CBP positivity. CBP deficiency or SR was common in endometrioid endometrial carcinoma (22.8 %), hepatocellular carcinoma (19.0 %), urothelial carcinoma (up to 17.4 %), serous endometrial carcinoma (12.5 %), and chromophobe renal cell carcinoma (RCC; 10.7 %). Less than 10 % CBP deficient or SR cases were seen in >50 additional tumor categories. Among tumors with CBP expression, reduced expression was linked to high pT (p < 0.0001), high UICC stage (p = 0.0005) and poor grade (p < 0.0001) in clear cell RCC, high UICC stage (p = 0.0409) and distant metastasis (p = 0.0022) in papillary RCC, advanced pT stage (p = 0.0003) in colorectal carcinoma and invasive disease (p < 0.0001) and L1 status (p = 0.0154) in urothelial carcinoma. High CBP expression was related to nodal metastasis in pancreatic adenocarcinoma (p = 0.0201). In conclusion, CBP deficiency is a rare event in many different tumor types. Reduced or absent CBP expression is linked to aggressive cancer phenotypes.

CBP （creb结合蛋白）是一种普遍表达的主要组蛋白修饰因子，参与数千种基因的调控。在癌症中，可能会发生功能丧失和过度表达。为了明确CBP表达的作用，我们用免疫组织化学方法分析了包含134种不同肿瘤实体的14966个样本和76种不同正常组织的608个样本的组织芯片。在正常组织中，除少数细胞类型外，普遍可见强核CBP染色。在12255例可评估的肿瘤中，226例（1.84%）CBP染色完全缺失（CBP缺乏），232例（1.89%）显示少数癌细胞仅呈微弱至中度染色（实质性减少，SR）， 384例（3.13%）弱，3079例（25.12%）中度，8334例（68.00%）强CBP阳性。CBP缺乏或SR在子宫内膜样子宫内膜癌（22.8%）、肝细胞癌（19.0%）、尿路上皮癌（高达17.4%）、浆液性子宫内膜癌（12.5%）和憎色性肾细胞癌（10.7%）中很常见。在另外50种肿瘤类别中，CBP缺陷或SR病例不到10%。在CBP表达的肿瘤中，表达减少与透明细胞RCC的高pT （p < 0.0001）、高UICC分期（p = 0.0005）和低分级（p < 0.0001）、乳头状RCC的高UICC分期（p = 0.0409）和远处转移（p = 0.0022）、结直肠癌和侵袭性疾病的晚期pT分期（p = 0.0003）和尿路上皮癌的L1状态（p = 0.0154）有关。CBP高表达与胰腺腺癌淋巴结转移相关（p = 0.0201）。总之，CBP缺乏在许多不同的肿瘤类型中是罕见的。CBP表达的减少或缺失与侵袭性癌症表型有关。

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引用次数: 0

Corrigendum to “Upregulation of CDK7 in gastric cancer cell promotes tumor cell proliferation and predicts poor prognosis” [Experimental and Molecular Pathology 100 (2016) 514–521] “胃癌细胞CDK7上调促进肿瘤细胞增殖并预测预后不良”[实验与分子病理学100(2016)514-521]更正。

IF 3.7 4区医学 Q2 PATHOLOGY

Experimental and molecular pathology

Pub Date : 2025-12-01 DOI: 10.1016/j.yexmp.2025.104974

Qiuhong Wang , Manhua Li , Xunlei Zhang , Hua Huang , Jianfei Huang , Jing Ke , Haifang Ding , Jinzhang Xiao , Xiaohang Shan , Qingqing Liu , Bojun Bao , Lei Yang

引用次数: 0

SUMOylation and NEDDylation in kidney diseases 肾脏疾病中的SUMOylation和neddyylation

IF 3.7 4区医学 Q2 PATHOLOGY

Experimental and molecular pathology

Pub Date : 2025-11-21 DOI: 10.1016/j.yexmp.2025.105010

Zi-Han Chen , Dan Li , Jian-Yu Zhang , Bo-Yu Wei , Hai-Ling Zhao , Ping Li , Dan-Qian Chen

Kidney disease poses a serious threat to human health and life, while the lack of specific therapeutic targets hinders the treatment of kidney disease. Emerging evidence shows that post-translational modifications (PTMs), particularly SUMOylation and NEDDylation, two ubiquitin-like modifications, are potential therapeutic targets for kidney disease. SUMOylation and NEDDylation participate in the treatment of kidney diseases by regulating different substrate proteins and signaling pathways. In renal ischemia-reperfusion injury, the promotion of LKB1 SUMOylation and the inhibition of NEDDylation modification facilitate renal fibrosis, and the increase of HIF-1α deSUMOylation contributes to attenuating apoptosis and oxidative stress in the kidneys. In diabetic kidney disease (DKD), the suppression of IKKγ SUMOylation attenuates NF-κB inflammatory signaling, while the inhibition of STAT1 SUMOylation and RBMX SUMOylation alleviates renal fibrosis. Additionally, inhibiting Notch1 signaling SUMOylation reduces podocyte apoptosis and glomerular endothelial cell injury, while the suppression of RhoA NEDDylation decreases inflammation and fibrosis in DKD. Accumulated studies display the therapeutic effect of the activators and inhibitors of SUMOylation and NEDDylation against kidney diseases, such as TAK-981 and MLN4924. Therefore, SUMOylation and NEDDylation function as promising therapeutic targets for kidney diseases, and their activators and inhibitors may serve as novel candidates.

肾脏疾病严重威胁着人类的健康和生命，而缺乏特异性的治疗靶点阻碍了肾脏疾病的治疗。新出现的证据表明，翻译后修饰（PTMs），特别是SUMOylation和neddyylation，两种泛素样修饰，是肾脏疾病的潜在治疗靶点。SUMOylation和neddyylation通过调节不同的底物蛋白和信号通路参与肾脏疾病的治疗。在肾缺血再灌注损伤中，LKB1的summoylation的促进和neddyylation修饰的抑制促进了肾纤维化，HIF-1α deSUMOylation的增加有助于减轻肾脏的凋亡和氧化应激。在糖尿病肾病（DKD）中，IKKγ summo酰化的抑制可减弱NF-κB炎症信号，而STAT1 summo酰化和RBMX summo酰化的抑制可减轻肾纤维化。此外，抑制Notch1信号summoylation可减少足细胞凋亡和肾小球内皮细胞损伤，而抑制RhoA NEDDylation可减少DKD中的炎症和纤维化。积累的研究显示SUMOylation和neddyylation的激活剂和抑制剂对肾脏疾病的治疗作用，如TAK-981和MLN4924。因此，SUMOylation和neddyylation是肾脏疾病的有希望的治疗靶点，它们的激活剂和抑制剂可能是新的候选物。

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引用次数: 0

Persistent renin-angiotensin system and inflammatory dysregulation following COVID-19 impairs ischemic stroke recovery COVID-19后持续肾素-血管紧张素系统和炎症失调损害缺血性卒中恢复

IF 3.7 4区医学 Q2 PATHOLOGY

Experimental and molecular pathology

Pub Date : 2025-11-20 DOI: 10.1016/j.yexmp.2025.105009

Amy May Lin Quek , Ooiean Teng , Ju-Hea Park , Bernadette Guek Cheng Er , Erle Chuen Hian Lim , Raymond Chee Seong Seet

Previous studies indicate that stroke recovery is worse in patients with prior COVID-19, suggesting persistent biological perturbations. We investigated lingering renin-angiotensin system (RAS) and inflammatory alterations after COVID-19 to uncover mechanisms driving impaired ischemic stroke recovery. We conducted a prospective observational cohort study comparing clinical and molecular profiles of ischemic stroke patients with and without recent COVID-19 infection to age-matched healthy controls. Plasma angiotensin-(1–7), angiotensin II, and soluble ACE2 were quantified, high-throughput proteomic profiling was performed using the Olink® Explore platform, and RNA sequencing was conducted to identify molecular mechanisms related to COVID-19-associated stroke and stroke outcomes (90-day modified Rankin Scale (mRS)). A total of 189 participants (38 COVID-19-associated stroke, 77 non-COVID-19 stroke, and 74 healthy controls) were enrolled. COVID-19-associated stroke patients exhibited significantly higher proportions of cryptogenic strokes (21.1 % vs 10.4 %), earlier hospital presentation (mean 185 vs 310 min), greater use of endovascular thrombectomy (97.4 % vs. 52.6 %), yet poorer functional outcomes (mRS ≥3) at 3 months (73 % vs. 47 %, all p < 0.05). Both stroke groups showed elevated angiotensin-(1–7) levels compared to controls, but angiotensin II levels were notably higher only in non-COVID-19 stroke patients. Proteomic analysis revealed sustained elevation of interferon-gamma (IFN-γ) signaling in COVID-19-associated stroke patients. Reduced AKT3 levels emerged as a significant predictor of poor outcomes, independent of renin-angiotensin biomarkers (adjusted OR 0.40; 95 % CI 0.16–0.94). Stroke patients with low AKT3 levels and poor outcomes exhibited significant upregulation of ribosomal proteins (RPS15, RPS4X, RPS7, RPS18, RPSA, RPS27A, RPS13, RPS23), reflecting heightened translational stress. Persistent RAS and inflammatory dysregulation following COVID-19 may contribute to worse stroke recovery. Future studies should validate and investigate the therapeutic implications of these findings.

先前的研究表明，先前感染COVID-19的患者中风恢复更差，这表明存在持续的生物学干扰。我们研究了COVID-19后持续存在的肾素-血管紧张素系统（RAS）和炎症改变，以揭示缺血性卒中恢复受损的机制。我们进行了一项前瞻性观察队列研究，比较了近期感染和未感染COVID-19的缺血性卒中患者与年龄匹配的健康对照者的临床和分子特征。定量血浆血管紧张素-(1-7)、血管紧张素II和可溶性ACE2，使用Olink®Explore平台进行高通量蛋白质组学分析，并进行RNA测序以确定与covid -19相关的卒中和卒中结局（90天改良Rankin量表（mRS））相关的分子机制。共纳入189名参与者（38名与covid -19相关的卒中，77名非covid -19卒中和74名健康对照）。与covid -19相关的卒中患者在3个月时表现出更高的隐源性卒中比例（21.1%对10.4%），更早的住院时间（平均185分钟对310分钟），更多的血管内取栓术（97.4%对52.6%），但更差的功能结局（mRS≥3）(73%对47%，均p

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引用次数: 0

Prospective evaluation of copy number alterations validates chromosome 1q gain as an independent marker of poor prognosis in localized Ewing sarcoma 拷贝数改变的前瞻性评估验证了染色体1q增益是局部尤文氏肉瘤预后不良的独立标志。

IF 3.7 4区医学 Q2 PATHOLOGY

Experimental and molecular pathology

Pub Date : 2025-11-17 DOI: 10.1016/j.yexmp.2025.105008

Juan Díaz-Martín , Andreas Ranft , Maite Blanquer-Maceiras , Rosa Noguera , Carmen Salguero-Aranda , Daniel Delgado-Bellido , Laura Romero-Pérez , Uta Dirksen , Enrique de Álava

Background

Ewing sarcoma is a rare and aggressive tumor affecting mainly adolescents and young adults. Accurate risk stratification is critical for treatment tailoring, yet traditional clinical parameters lack sufficient predictive accuracy. While retrospective studies have identified potential molecular biomarkers, prospective validation is required for clinical implementation.

Methods

The international PROVABES consortium (PROspective Validation of Biomarkers in Ewing Sarcoma) aims to evaluate molecular prognostic markers in European patients treated under international phase III trials. This study focuses on copy number alterations (CNAs), in 305 primary tumors. Tissue microarrays were analyzed by FISH for chromosome 1q gain (n = 297) and 16q loss (n = 266). Genome-wide CNAs were further assessed using SNP arrays in 139 samples. Associations with clinical outcomes were evaluated via Kaplan-Meier and multivariate Cox regression, with event-free survival (EFS) and overall survival (OS) as endpoints.

Results

Chromosome 1q gain was significantly associated with shorter OS in both localized cases and the overall cohort, and with inferior EFS specifically in localized patients. In contrast, 16q loss showed no significant prognostic impact. Multivariate analysis confirmed 1q gain as an independent predictor of poor EFS in localized disease. Notably, a higher fraction of genome altered was associated with inferior OS and EFS not only in localized patients but also in the entire cohort, and remained an independent predictor of outcome despite the smaller subset analyzed.

Conclusions

This prospective study validates chromosome 1q gain as an independent marker of poor prognosis in localized Ewing sarcoma. Furthermore, the extent of genomic alteration emerges as a promising predictor of both OS and EFS. Incorporating these biomarkers may improve individualized risk stratification and ultimately enhance patient outcomes.

背景：尤文氏肉瘤是一种罕见的侵袭性肿瘤，主要影响青少年和青壮年。准确的风险分层是治疗的关键，但传统的临床参数缺乏足够的预测准确性。虽然回顾性研究已经确定了潜在的分子生物标志物，但临床实施需要前瞻性验证。方法：国际PROVABES联盟（尤因肉瘤生物标志物的前瞻性验证）旨在评估在国际III期试验中治疗的欧洲患者的分子预后标志物。本研究的重点是305种原发肿瘤的拷贝数改变（CNAs）。用FISH分析组织微阵列中染色体1q增加（n = 297）和16q丢失（n = 266）。在139个样本中使用SNP阵列进一步评估全基因组CNAs。以无事件生存期（EFS）和总生存期（OS）为终点，通过Kaplan-Meier和多变量Cox回归评估与临床结果的相关性。结果：染色体1q增加与局部病例和整体队列中较短的OS显著相关，并与局部患者较低的EFS特异性相关。相比之下，16q的损失对预后没有显著影响。多变量分析证实1q增益是局部疾病EFS差的独立预测因子。值得注意的是，不仅在局部患者中，而且在整个队列中，较高比例的基因组改变与较差的OS和EFS相关，尽管分析的子集较小，但仍然是结果的独立预测因子。结论：本前瞻性研究证实染色体1q增加是局部尤文氏肉瘤预后不良的独立标志。此外，基因组改变的程度是预测OS和EFS的一个很有希望的指标。结合这些生物标志物可以改善个体化的风险分层，最终提高患者的预后。

{"title":"Prospective evaluation of copy number alterations validates chromosome 1q gain as an independent marker of poor prognosis in localized Ewing sarcoma","authors":"Juan Díaz-Martín , Andreas Ranft , Maite Blanquer-Maceiras , Rosa Noguera , Carmen Salguero-Aranda , Daniel Delgado-Bellido , Laura Romero-Pérez , Uta Dirksen , Enrique de Álava","doi":"10.1016/j.yexmp.2025.105008","DOIUrl":"10.1016/j.yexmp.2025.105008","url":null,"abstract":"<div><h3>Background</h3><div>Ewing sarcoma is a rare and aggressive tumor affecting mainly adolescents and young adults. Accurate risk stratification is critical for treatment tailoring, yet traditional clinical parameters lack sufficient predictive accuracy. While retrospective studies have identified potential molecular biomarkers, prospective validation is required for clinical implementation.</div></div><div><h3>Methods</h3><div>The international PROVABES consortium (PROspective Validation of Biomarkers in Ewing Sarcoma) aims to evaluate molecular prognostic markers in European patients treated under international phase III trials. This study focuses on copy number alterations (CNAs), in 305 primary tumors. Tissue microarrays were analyzed by FISH for chromosome 1q gain (<em>n</em> = 297) and 16q loss (<em>n</em> = 266). Genome-wide CNAs were further assessed using SNP arrays in 139 samples. Associations with clinical outcomes were evaluated via Kaplan-Meier and multivariate Cox regression, with event-free survival (EFS) and overall survival (OS) as endpoints.</div></div><div><h3>Results</h3><div>Chromosome 1q gain was significantly associated with shorter OS in both localized cases and the overall cohort, and with inferior EFS specifically in localized patients. In contrast, 16q loss showed no significant prognostic impact. Multivariate analysis confirmed 1q gain as an independent predictor of poor EFS in localized disease. Notably, a higher fraction of genome altered was associated with inferior OS and EFS not only in localized patients but also in the entire cohort, and remained an independent predictor of outcome despite the smaller subset analyzed.</div></div><div><h3>Conclusions</h3><div>This prospective study validates chromosome 1q gain as an independent marker of poor prognosis in localized Ewing sarcoma. Furthermore, the extent of genomic alteration emerges as a promising predictor of both OS and EFS. Incorporating these biomarkers may improve individualized risk stratification and ultimately enhance patient outcomes.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"144 ","pages":"Article 105008"},"PeriodicalIF":3.7,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145549016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Histopathological analysis reveals mild to moderate changes in BALB/c mice after short-term administration of a microemulsion loaded with epoxy-α-lapachone 组织病理学分析显示，短期给药环氧-α-lapachone微乳后BALB/c小鼠出现轻度至中度变化。

IF 3.7 4区医学 Q2 PATHOLOGY

Experimental and molecular pathology

Pub Date : 2025-10-31 DOI: 10.1016/j.yexmp.2025.105006

Luiz Filipe Gonçalves-Oliveira , Juliana Figueiredo Peixoto , Bernardo Acácio Santini Pereira , Nathalia Silva Carlos Oliveira , Flávia de Oliveira Cardoso , Davyson de Lima Moreira , Franklin Silva-Souza , Carlos Roberto Alves

The development of innovative treatments for American Cutaneous Leishmaniasis is crucial due to severe side effects of current treatment and the emergence of non-responder parasites. To address such a challenge the incorporation of epoxy-α-lapachone (ELAP) into a microemulsion (ME), named ELAP-ME, represents a promising therapeutic approach. In previous studies, ELAP-ME demonstrated efficacy in controlling infection in the BALB/c-Leishmania (Leishmania) amazonensis model, advancing in the technology readiness level with a drug prototype. To further validate its potential as a drug prototype, the histopathological effects of ELAP-ME were investigated in healthy BALB/c mice as a preclinical approach stage. Mice were administered with a fixed dose of ELAP-ME microemulsion (∼7 μg/kg) and evaluated at different short-term after administration (4, 12, and 24 h). Histopathological analysis of the liver, kidney, lung, heart, and brain revealed only mild alterations. These findings confirm the low toxicity profile of ELAP-ME, highlighting its safety and supporting its continued advancement as a pharmacological alternative for the treatment of leishmaniasis.

由于目前治疗的严重副作用和无反应寄生虫的出现，开发美国皮肤利什曼病的创新治疗方法至关重要。为了解决这一挑战，将环氧-α-拉帕酮（ELAP）掺入微乳液（ME）中，称为ELAP-ME，是一种很有前景的治疗方法。在之前的研究中，ELAP-ME在BALB/c-亚马逊利什曼原虫模型中显示出控制感染的有效性，并在药物原型的技术就绪水平上取得了进展。为了进一步验证其作为药物原型的潜力，ELAP-ME在健康BALB/c小鼠中作为临床前研究阶段进行了组织病理学研究。给小鼠注射固定剂量的ELAP-ME微乳（~ 7 μg/kg），并在给药后的不同时间内（4、12和24 h）进行评价。肝、肾、肺、心和脑的组织病理学分析显示只有轻微的改变。这些发现证实了ELAP-ME的低毒性，强调了其安全性，并支持其作为治疗利什曼病的替代药物的持续发展。

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引用次数: 0

RBFOX2: An RNA-binding protein with alternative splicing and non-alternative splicing regulatory functions RBFOX2：一种具有选择性剪接和非选择性剪接调节功能的rna结合蛋白。

IF 3.7 4区医学 Q2 PATHOLOGY

Experimental and molecular pathology

Pub Date : 2025-10-30 DOI: 10.1016/j.yexmp.2025.105007

Wei Wang , Yang Zhang , Siyi Liu , Shan Liao , Junyu He , Gengqiu Luo , Qian He , Yanhong Zhou

RNA-binding Fox-1 homolog 2 (RBFOX2) is a key RNA-binding protein that primarily functions by regulating alternative splicing. Furthermore, RBFOX2 regulates RNA metabolism across the transcriptional and multiple post-transcriptional stages, encompassing recognizing RNA epigenetic modifications, inhibiting transcription, regulating alternative polyadenylation, inhibiting miRNA processing, and stabilizing mRNA. Additionally, RBFOX2 is regulated by upstream factors such as RNA binding proteins, non-coding RNAs, and transcription factors. RBFOX2 is extensively involved in the regulation of development and the maintenance of physiological functions. The dysregulation of RBFOX2 is closely associated with tumors, cardiovascular diseases, developmental defects and metabolic diseases. In this review, we summarize the regulatory functions of RBFOX2 in terms of both alternative and non-alternative splicing, the upstream regulatory factors of RBFOX2, and its relationship with disease etiology and progression, with the aim of providing a comprehensive understanding of the role of RBFOX2 and offering new insights for the study of RBFOX2.

RNA-binding Fox-1同源物2 （RBFOX2）是一种关键的rna结合蛋白，主要通过调节选择性剪接起作用。此外，RBFOX2在转录和多个转录后阶段调节RNA代谢，包括识别RNA表观遗传修饰、抑制转录、调节选择性多聚腺苷化、抑制miRNA加工和稳定mRNA。此外，RBFOX2还受上游因子如RNA结合蛋白、非编码RNA和转录因子的调控。RBFOX2广泛参与发育调控和生理功能维持。RBFOX2的失调与肿瘤、心血管疾病、发育缺陷和代谢性疾病密切相关。本文就RBFOX2在选择性剪接和非选择性剪接方面的调控功能、RBFOX2的上游调控因子及其与疾病病因和进展的关系进行综述，以期全面了解RBFOX2的作用，并为RBFOX2的研究提供新的见解。

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引用次数: 0

High KCNJ14 expression is associated with an immunosuppressive tumor microenvironment and advanced pathological features: An RNA in situ hybridization-based analysis of colorectal carcinoma KCNJ14高表达与免疫抑制肿瘤微环境和晚期病理特征相关：基于RNA原位杂交的结直肠癌分析

IF 3.7 4区医学 Q2 PATHOLOGY

Experimental and molecular pathology

Pub Date : 2025-10-21 DOI: 10.1016/j.yexmp.2025.105005

Hiroshi Sawaguchi , Takeshi Uehara , Mai Iwaya , Shiho Asaka , Tomoyuki Nakajima , Shotaro Komamura , Shunsuke Imamura , Yugo Iwaya , Shinsuke Sugenoya , Masato Kitazawa , Yuji Soejima , Hiroyoshi Ota , Tadanobu Nagaya

Colorectal carcinoma (CRC) remains one of the leading causes of cancer-related deaths worldwide, and there is a lack of reliable biomarkers to predict tumor progression and the immune microenvironment. KCNJ14 is a member of the inwardly rectifying potassium channel family that has recently been implicated in tumor progression and immune suppression; however, its clinical significance and spatial expression patterns in CRC remain unclear. We evaluated KCNJ14 mRNA expression by RNA in situ hybridization using an RNAscope on a tissue microarray of 259 CRC cases. We assessed the associations between KCNJ14 expression and clinicopathological features, tumor-infiltrating CD4⁺, CD8⁺, and FOXP3⁺ cells, and patient outcomes. We also performed single-cell RNA sequencing analysis to determine the cell type-specific expression of KCNJ14. KCNJ14 expression was predominantly observed in cancer cells, with high expression identified in 36 cases. High KCNJ14 expression was significantly associated with lymphatic invasion, venous invasion, lymph node metastasis, and advanced disease stage. High KCNJ14 expression was also correlated with decreased intratumoral infiltration of CD4⁺ and CD8⁺ T cells, as well as lower tumor-infiltrating lymphocyte scores, indicating an immunosuppressive tumor microenvironment. In contrast, there were no significant associations between KCNJ14 expression and FOXP3⁺ cell infiltration, overall survival, or recurrence-free survival. This study is the first to demonstrate that high KCNJ14 expression is associated with an immunosuppressive tumor microenvironment and advanced pathological features in CRC. Although KCNJ14 is not an independent prognostic factor, it may serve as a potential indicator of an immunosuppressive tumor microenvironment and be a novel therapeutic target.

结直肠癌（CRC）仍然是全球癌症相关死亡的主要原因之一，缺乏可靠的生物标志物来预测肿瘤进展和免疫微环境。KCNJ14是内矫正钾通道家族的成员，最近被认为与肿瘤进展和免疫抑制有关；然而，其在结直肠癌中的临床意义和空间表达模式尚不清楚。我们使用RNAscope对259例结直肠癌患者的组织微阵列进行RNA原位杂交，评估了KCNJ14 mRNA的表达。我们评估了KCNJ14表达与临床病理特征、肿瘤浸润性CD4+、CD8+和FOXP3+细胞以及患者预后之间的关系。我们还进行了单细胞RNA测序分析，以确定KCNJ14的细胞类型特异性表达。KCNJ14主要在癌细胞中表达，在36例中发现高表达。KCNJ14高表达与淋巴浸润、静脉浸润、淋巴结转移和疾病晚期相关。KCNJ14高表达还与肿瘤内CD4+和CD8+ T细胞浸润减少以及肿瘤浸润淋巴细胞评分降低相关，表明肿瘤微环境具有免疫抑制作用。相比之下，KCNJ14表达与FOXP3+细胞浸润、总生存期或无复发生存期之间没有显著相关性。本研究首次证明KCNJ14高表达与CRC的免疫抑制肿瘤微环境和晚期病理特征相关。虽然KCNJ14不是一个独立的预后因素，但它可能作为免疫抑制肿瘤微环境的潜在指标，成为一个新的治疗靶点。

{"title":"High KCNJ14 expression is associated with an immunosuppressive tumor microenvironment and advanced pathological features: An RNA in situ hybridization-based analysis of colorectal carcinoma","authors":"Hiroshi Sawaguchi , Takeshi Uehara , Mai Iwaya , Shiho Asaka , Tomoyuki Nakajima , Shotaro Komamura , Shunsuke Imamura , Yugo Iwaya , Shinsuke Sugenoya , Masato Kitazawa , Yuji Soejima , Hiroyoshi Ota , Tadanobu Nagaya","doi":"10.1016/j.yexmp.2025.105005","DOIUrl":"10.1016/j.yexmp.2025.105005","url":null,"abstract":"<div><div>Colorectal carcinoma (CRC) remains one of the leading causes of cancer-related deaths worldwide, and there is a lack of reliable biomarkers to predict tumor progression and the immune microenvironment. <em>KCNJ14</em> is a member of the inwardly rectifying potassium channel family that has recently been implicated in tumor progression and immune suppression; however, its clinical significance and spatial expression patterns in CRC remain unclear. We evaluated <em>KCNJ14</em> mRNA expression by RNA in situ hybridization using an RNAscope on a tissue microarray of 259 CRC cases. We assessed the associations between <em>KCNJ14</em> expression and clinicopathological features, tumor-infiltrating CD4<sup>+</sup>, CD8<sup>+</sup>, and FOXP3<sup>+</sup> cells, and patient outcomes. We also performed single-cell RNA sequencing analysis to determine the cell type-specific expression of <em>KCNJ14</em>. <em>KCNJ14</em> expression was predominantly observed in cancer cells, with high expression identified in 36 cases. High <em>KCNJ14</em> expression was significantly associated with lymphatic invasion, venous invasion, lymph node metastasis, and advanced disease stage. High <em>KCNJ14</em> expression was also correlated with decreased intratumoral infiltration of CD4<sup>+</sup> and CD8<sup>+</sup> T cells, as well as lower tumor-infiltrating lymphocyte scores, indicating an immunosuppressive tumor microenvironment. In contrast, there were no significant associations between <em>KCNJ14</em> expression and FOXP3<sup>+</sup> cell infiltration, overall survival, or recurrence-free survival. This study is the first to demonstrate that high <em>KCNJ14</em> expression is associated with an immunosuppressive tumor microenvironment and advanced pathological features in CRC. Although <em>KCNJ14</em> is not an independent prognostic factor, it may serve as a potential indicator of an immunosuppressive tumor microenvironment and be a novel therapeutic target.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"144 ","pages":"Article 105005"},"PeriodicalIF":3.7,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0